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. 2018 Jul 20;9(7):735. doi: 10.1038/s41419-018-0765-9

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 9 — a Representative images of a mtDNA-depleter mouse showing skin wrinkles and hair loss after 2 months of continuous dox induction (+dox; mtDNA depletion) (ii) and reversal of these phenotypic changes after 1 month of dox withdrawal (−dox; mtDNA repletion) (iii; n = 3). Wild-type control mice (n = 3) did not show any change in skin phenotype after dox treatment or after 1 month of dox withdrawal (i). b Hematoxylin- and eosin-stained sections of dorsal skin from wild-type control mice (i), mtDNA-depleter mice after 2 months of continuous dox induction (mtDNA depletion) (ii) and after 1 month of dox withdrawal (mtDNA repletion) (iii). c Giemsa staining of skin sections shows the presence of increased number of mast cells in the dermis and perifollicular as well as near-epidermal locations of mtDNA-depleter mice compared with skin sections of wild-type mice. Compared with mtDNA-depleter mice, the lower number of mast cells is present in the skin of mtDNA-depleter mice after 1 month of dox withdrawal (−dox; mtDNA repletion). Arrows indicate the presence of Giemsa-positive cells in the skin sections. d–f Quantification of epidermal thickness (d), hair follicles in telogen (e), and anagen (f) stages of hair cycles (mean ± s.e.m; *P<0.05, Student’s t test) in skin samples from wild-type control (n = 3) and mtDNA-depleter (n = 3) mice after 2 months of continuous dox induction (mtDNA depletion) and after 1 month of dox withdrawal (mtDNA repletion). g Quantitative analysis of Giemsa-positive mast cells in the skin sections of wild-type control, mtDNA-depleter mice after 2 months of continuous dox induction (mtDNA depletion), and after 1 month of dox withdrawal (mtDNA repletion) (mean ± s.e.m; *P<0.05, Student’s t test). h Quantification of mtDNA content (mean ± s.e.m; *P<0.05, Student’s t test) in skin samples from wild-type control (n = 3) and mtDNA-depleter (n = 3) mice after 2 months of continuous dox induction and reversal of mtDNA content in skin samples of mtDNA-depleter mice (n = 3) after 1 month of dox withdrawal. i, j Representative gel images showing RT-PCR analysis of genes in the skin RNA samples of wild-type control (n = 3) and mtDNA-depleter mice (n = 3) after 1 month of dox withdrawal (mtDNA repletion). Depletion = mtDNA depletion, repletion = mtDNA repletion